Anti-Xa Activity of Enoxaparin for Prevention of Venous Thromboembolism in Severe Nephrotic Syndrome. (ENOX-inNS)

Assessment of Coagulation Disorders and of Enoxaparin's Anti-Xa Activity, When Used for Thromboprophylaxis, in Severe Nephrotic Syndrome.

The primary objective is to test the hypothesis that enoxaparin efficacy is reduced in severe nephrotic syndrome. Another purpose is to compare two dosing regimens.

Study Overview

• Status: Terminated
• Conditions: Nephrotic Syndrome
• Intervention / Treatment: Drug: Enoxaparin

Detailed Description

Nephrotic syndrome (NS) is a rare clinical condition characterized by proteinuria exceeding >3.5 g/24h, hypoalbuminemia, dyslipidemia and edema and is associated with hypercoagulable state. In severe cases, with serum albumin ≤2.5 g/dL, the risk of venous thromboembolic events (VTE) is particularly high, and pharmacological prophylaxis is recommended. However, there is a limited evidence of its efficacy and optimal dosing.

The study is designed as 3 arms clinical trial, with 2 study groups and a single control group. The study groups will include patients with severe NS parallelly, alternately assigned (1:1) into two enoxaparin dosing regimens. The control group will consisted of individuals without proteinuria and edema, similar in terms of age, anthropometric features and renal function to NS patients, who will be administered a standard enoxaparin dose. A peak anti-Xa activity at the steady state will be measured to determine the plasma concentration of enoxaparin. Additional laboratory tests for markers of NS severity, renal function and coagulation system proteins will be performed. The overhydration and body water compartments will be assessed using bioimpedance spectroscopy technique. Nephrotic patients will be followed up by 12 months to assess overt VTE and adverse events associated with enoxaparin use.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Poland
  • Masovian District
    • Warsaw, Masovian District, Poland, 04-141
      • Military Institute of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Severe NS, defined as proteinuria exceeding 3.5 g/24h or 50 mg/kg/24h and serum albumin ≤2.5 g/dL;
• eGFR ≥30 mL/min/1.73 m2.

Exclusion Criteria:

• Body mass index (BMI) ≥40 kg/m2;
• Low body mass (<45 kg for female, <57 kg for male);
• Acute VTE;
• Previously introduced anticoagulation (due to comorbidities);
• Contraindications for enoxaparin;
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nephrotic syndrome - fixed dose (NS-FD); Drug: Enoxaparin; Dose: 40 mg; Administration: once daily subcutaneously.	Drug: Enoxaparin
Experimental: Nephrotic syndrome - adjusted dose (NS-AD); Drug: Enoxaparin; Dose: 1 mg/kg of ideal body weight; Administration: once daily subcutaneously.	Drug: Enoxaparin
Active Comparator: Control - fixed dose (C-FD); Drug: Enoxaparin; Dose: 40 mg; Administration: once daily subcutaneously.	Drug: Enoxaparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic enoxaparin's anti-Xa activity in nephrotic syndrome.	Anti-Xa activity values ≥ 0.3 IU/mL in the steady state of enoxaparin concentration, on average between days 3 and 5.	Average: Day 3-5
Minimum threshold of enoxaparin's anti-Xa activity.	Anti-Xa activity values ≥ 0.2 IU/mL in the steady state of enoxaparin concentration on average between days 3 and 5.	Average: Day 3-5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of nephrotic syndrome.	Serum or/and urinary concentration of laboratory markers of disease.	Day 0, Day 3-5
Coagulation system protein.	Plasma concentration or activity of secondary hemostasis system protein (clotting factors, fibrinolysis factors, regulatory molecules).	Day 0, Day 3-5
Renal function.	Estimated glomerular filtration rate (eGFR) calculated with simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula.	Day 0, Day 3-5
Edema.	Clinical evaluation of edema using 3-stages scale (I: <5 kg, II: 5-10 kg, III: >10 kg) at enrollment and on the day of measuring anti-Xa activity of enoxaparin.	Day 0, Day 3-5
Overhydration.	Overhydration measured by bioimpedance spectroscopy on the day of measuring anti-Xa activity of enoxaparin.	Day 3-5

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Venous thromboembolic events.	Clinically overt episode of VTE.	Follow-up period of 1 year from enrollment.
Adverse events of enoxaparin.	Episodes of minor and major bleeding or heparin-induced thrombocytopenia.	Follow-up period of 1 year from enrollment.

Collaborators and Investigators

• Sponsor: Military Institute of Medicine, Poland
• Investigators: Principal Investigator: Anna Matyjek, MD, PhD, Military Institute of Medicine

Publications and helpful links

General Publications

• Matyjek A, Rymarz A, Nowicka Z, Literacki S, Rozmyslowicz T, Niemczyk S. Anti-Xa Activity of Enoxaparin for Prevention of Venous Thromboembolism in Severe Nephrotic Syndrome-A Single Center Prospective Study. J Clin Med. 2021 Dec 6;10(23):5709. doi: 10.3390/jcm10235709.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: September 10, 2020
• First Submitted That Met QC Criteria: September 16, 2020
• First Posted (Actual): September 22, 2020

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Low molecular weight heparin; Enoxaparin; Venous thromboembolism; Nephrotic syndrome; Anti-Xa activity; Antifactor Xa
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Kidney Diseases; Urologic Diseases; Disease; Embolism and Thrombosis; Syndrome; Thromboembolism; Venous Thromboembolism; Nephrotic Syndrome; Nephrosis; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Enoxaparin
• Other Study ID Numbers: 5/8952 (443)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No